MEK*

Protein MEK*

Identifiers
HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750 GENECARDS:MAP2K1 HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507 GENECARDS:MAP2K2
mitogen-activated protein kinase kinase 1
PRKMK1
HUGO:MAP2K1 HGNC:6840 ENTREZ:5604 UNIPROT:Q02750
mitogen-activated protein kinase kinase 2
PRKMK2
HUGO:MAP2K2 HGNC:6842 ENTREZ:5605 UNIPROT:P36507

Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK

References
PMID:24027568 PMID:9510155 PMID:14764585 PMID:15735649
REACTOME:59503 KEGG:5604 ATLASONC:GC_MAP2K1 WIKI:MAP2K1
REACTOME:59505 KEGG:5605 ATLASONC:GC_MAP2K2 WIKI:MAP2K2
NATURAL_KILLER
CASCADE:NKP46
CASCADE:Fc_gamma_RIII
CASCADE:TLR2_4
PMID:11062502, PMID:11385609, PMID:11907067, PMID:15536084
Nkp46 controls NK cytolitic activity via PI3K /RAC1/PAK1/MEK??/ERK pathway, probably throught SYK
PMID:17395718, PMID:11062502, PMID:??15536084
PAK1 activates classical MEK/ERK cascad resulted in granule movement and polarization and tumor cel lysis downstream of Nkp30, Syk and PI3K.
PMID:10843677
IL2 activates MEK (MKK)/ERK pathway in NK cells.
MKK/ERK pathway is necessary for IL-2 to activate NK cells to express at least four known biological responses: LAK generation, IFN-gamma secretion, and CD25 and CD69 expression.
PMID:11034387
MAPK activation in NK cells resulted in lysis is Ras-independent.
PMID:22435554, PMID:15169888
In unstimulated cells, TPL-2 is con???ned to a cytoplasmic complex with
the NF-jB1 precursor protein p105, and the ubiquitin-binding protein ABIN-2.
Interactions with both p105 and ABIN-2 are required to maintain
TPL-2 protein stability, while TPL-2 association with p105 also inhibits TPL-2 phosphorylation of its substrates MEK-1???2
In resting cells MEK1/2 are localised in the cytoplasm and this may be induced by two molecular mechanisms (i.e.: the presence of a nuclear export domain (NES) in their N-terminal domain; the binding to cytoplasmic anchors such as KSR MP1 beta-ARRESTIN-2 Sef1).
MEK1 forms a complex with P14 and MP1 on late endosomes necessary for the activation of ERK pathway in this location of the cell.
MP1 specifically binds MEK1 and ERK1 but not MEK2 or ERK2. (Activation on late endosomes)
PMID:19565474 PMID:17178906 PMID:15547943

MEK*@Cytoplasm

References
su_mpk1_mpk1_re190( Survival ):
MEK is continuously dephosphorylated by PP2A (PPP2CA) whose activity is stimulated by P38: P38 activity increases the physical association between PP2A and MEK/ERK complex.
PMID:18039929
su_mpk1_mpk1_re18( Survival ):
Formation of P14/MP1/MEK1 complex is required to activate the ERK cascade (and other processes) on late endosomes.
PMID:17178906
su_mpk1_mpk1_re57( Survival ):
Sef1 which is a putative transmembrane protein of the Golgi apparatus seems to be a scaffold protein that recruits ERK1/2 and MEK1/2 to its vicinity and probably allows their activation by Golgi-localised Ras proteins.
PMID:19565474
su_mpk1_mpk1_re62( Survival ):
The component kinases of the ERK cascade Raf-1 MEK and ERK assemble using beta-ARRESTIN as a scaffold and leading to activation of ERK. Endocytosis of these receptor/beta-ARRESTIN complexes by clathrin-coated pits results in the targeting of activated ERK to endosomal vesicles.
The beta-ARRESTIN occupied receptor undergoes internalisation into early endosomes. At the early endosome stage beta-ARRESTIN recruits both MEK1/2 and ERK1/2 and is likely to facilitate their activation upon GPCR stimulation.
PMID:11226259 PMID:19565474
su_mpk1_mpk1_re186( Survival ):
MLK3 and MLK2 two MAP3Ks of JNK pathway can interact with RAC1 in a GTP-dependent manner.
MEKK2 and MEKK3 can activate JNK P38 and ERK pathways
MLK3 has the potential to positively regulate the ERK / MAPK pathway by directly phosphorylating and activating MEK.
PMID:11274345 PMID:12738796

MEK*|pho|pho@Cytoplasm

References
su_mpk1_mpk1_re186( Survival ):
MLK3 and MLK2 two MAP3Ks of JNK pathway can interact with RAC1 in a GTP-dependent manner.
MEKK2 and MEKK3 can activate JNK P38 and ERK pathways
MLK3 has the potential to positively regulate the ERK / MAPK pathway by directly phosphorylating and activating MEK.
PMID:11274345 PMID:12738796
su_mpk1_mpk1_re159:( Survival ) Any other mechanism of ERK activation not explicitly modelled.
su_mpk1_mpk1_re190( Survival ):
MEK is continuously dephosphorylated by PP2A (PPP2CA) whose activity is stimulated by P38: P38 activity increases the physical association between PP2A and MEK/ERK complex.
PMID:18039929

Modifications:
In compartment: Cytoplasm

MEK*@Cytoplasm
MEK*|pho|pho@Cytoplasm

In compartment: INNATE_IMMUNE_CELL_Cytosol

MEK*@INNATE_IMMUNE_CELL_Cytosol
MEK*|pho@INNATE_IMMUNE_CELL_Cytosol

In compartment: T_cell

MEK*@T_cell
MEK*|pho@T_cell

Participates in complexes:
In compartment: Cytoplasm

In compartment: Early Endosomes

In compartment: Golgi Apparatus

ERK*:MEK*:SEF*@Golgi Apparatus

In compartment: Late Endosomes

In compartment: Plasma Membrane

Participates in reactions:
As Reactant or Product:

As Catalyser: